New Pill Cuts Triglycerides 38% in Early Human Trial

A new pill has shown it can safely reduce dangerous blood fats in humans, offering hope to millions struggling with high triglycerides and related heart risks.

Scientists at EPFL and OrsoBio developed TLC-2716, an oral medication that specifically targets fat production in the liver and gut. The compound works differently from previous attempts by acting as an inverse agonist, essentially flipping a genetic switch called Liver X Receptor to reduce fat without disrupting beneficial cholesterol pathways elsewhere in the body.

High triglycerides affect millions worldwide and significantly increase the risk of heart disease, stroke, and pancreatitis. While diet and exercise help, many people need medication, but previous drug attempts either failed or caused harmful side effects by blocking protective cholesterol systems throughout the body.

The research team started by analyzing massive genetic datasets to identify which receptor variant drives high triglycerides. They found that LXRα, highly active in the liver, was the culprit. Armed with this knowledge, they tested TLC-2716 in lab models and saw impressive results: lower triglycerides, reduced liver fat, and decreased inflammation.

Safety testing in animals showed the drug stays mostly in the liver and gut, limiting exposure to other tissues where blocking LXR could cause problems. This tissue-specific action solved the main obstacle that has stalled similar drugs for years.

The Phase I human trial enrolled healthy adults who took TLC-2716 daily for 14 days. Even in this short window with participants who had normal lipid levels to start, the results were striking. At the highest dose, triglycerides dropped by 38.5%, and after-meal remnant cholesterol plummeted by 61%.

The drug worked by speeding up how quickly the body clears triglycerides, reducing activity of two proteins that normally slow the process. Importantly, researchers saw no reduction in markers linked to reverse cholesterol transport, the protective pathway that helps remove cholesterol from tissues.

Why This Inspires

This breakthrough represents the first human proof that selectively targeting liver fat production can work safely. For decades, scientists knew blocking LXR could help, but the risk of disrupting protective systems kept the approach off limits.

The tissue-specific design of TLC-2716 elegantly solves this puzzle. By concentrating the drug's action where fat problems start, it avoids interfering with beneficial processes elsewhere. This precision approach could open doors for treating not just high triglycerides but also related conditions like fatty liver disease.

The trial met all safety endpoints, and participants tolerated the medication well. Larger Phase II studies are now planned for people with diagnosed hypertriglyceridemia and metabolic liver disease, where the benefits could be even more dramatic.

After years of setbacks in this field, seeing dramatic lipid reductions in humans without safety concerns marks genuine progress toward a new treatment option that could complement existing therapies.